vspВопросы современной педиатрииCurrent Pediatrics1682-55271682-5535Издательство «ПедиатрЪ»10.15690/vsp.v15i5.1624vsp-1674Research ArticleОРИГИНАЛЬНАЯ СТАТЬЯORIGINAL ARTICLESЭФФЕКТИВНОСТЬ И БЕЗОПАСНОСТЬ РИТУКСИМАБА У ДЕТЕЙ С СИСТЕМНОЙ КРАСНОЙ ВОЛЧАНКОЙ: РЕЗУЛЬТАТЫ РЕТРОСПЕКТИВНОГО ИССЛЕДОВАНИЯ СЕРИИ СЛУЧАЕВEFFICACY AND SAFETY OF RITUXIMAB IN CHILDREN WITH SYSTEMIC LUPUS ERYTHEMATOSUS: RESULTS OF A RETROSPECTIVE STUDY OF THE CASE SERIESАлексееваЕ. И.AlexeevaEkaterina I.

Алексеева Екатерина Иосифовна - доктор медицинских наук, профессор, член-корр. РАН, заведующая ревматологическим отделением НЦЗД, декан педиатрического факультета Первого МГМУ имени И.М. Сеченова.

alekatya@yandex.ruДенисоваР. В.DenisovaRina V.ВалиеваС. И.ValievaSaniya I.БзароваТ. М.BzarovaTatyana M.СлепцоваТ. В.SleptsovaTatyana V.ЧомахидзеА. М.ChomakhidzeAlexandra M.ИсаеваК. Б.IsayevaKseniya B.ЧистяковаЕ. Г.ChystyakovaEvgeniya G.СемикинаЕ. Л.SemikinaElena L.Научный центр здоровья детей; Первый Московский государственный медицинский университет имени И.М. СеченоваРоссияScientific Center of Children’s Health; Sechenov First Moscow State Medical UniversityRussian FederationНаучный центр здоровья детейРоссияScientific Center of Children’s HealthRussian FederationНаучный центр здоровья детей; Первый Московский государственный медицинский университет имени И.М. СеченоваРоссияScientific Center of Children’s Health; Sechenov First Moscow State Medical UniversityRussian Federation201624112016155497504Copyright © Алексеева Е.И., Денисова Р.В., Валиева С.И., Бзарова Т.М., Слепцова Т.В., Чомахидзе А.М., Исаева К.Б., Чистякова Е.Г., Семикина Е.Л., 20162016Алексеева Е.И., Денисова Р.В., Валиева С.И., Бзарова Т.М., Слепцова Т.В., Чомахидзе А.М., Исаева К.Б., Чистякова Е.Г., Семикина Е.Л.Alexeeva E.I., Denisova R.V., Valieva S.I., Bzarova T.M., Sleptsova T.V., Chomakhidze A.M., Isayeva K.B., Chystyakova E.G., Semikina E.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vsp.spr-journal.ru/jour/article/view/1674

Блокирование В лимфоцитов, продуцирующих аутоантитела при системной красной волчанке (СКВ), может быть эффективной стратегией патогенетического лечения, в том числе и у детей.

Цель исследования

Цель исследования: оценить эффективность и безопасность терапии ритуксимабом (химерные моноклональные антитела к CD20) у детей с тяжелым течением СКВ, рефрактерной к глюкокортикостероидам и иммунодепрессантам. Методы. Изучали истории болезни детей с СКВ, госпитализированных в ревматологическое отделение НЦЗД в период с 2004 по 2013 г.

Результаты лечения оценивали по индексу активности болезни SELENA SLEDAI, шкале Damage Index, динамике значений лабораторных показателей активности болезни.

Результаты

Результаты. Проанализированы результаты лечения ритуксимабом 12 пациентов в течение 24 нед, 11 из них — в течение 48 нед. Препарат вводился внутривенно в дозе 375 мг/м2 стандартной поверхности тела на введение еженедельно 4 раза (n = 10) или 2 раза с интервалом 2 нед (n = 2). Через 48 нед терапии ритуксимабом значения индекса SELENA SLEDAI снизились с 16 (11, 21) до 1 (0, 2) (p < 0,001), Damage Index — c 3,5 (1,0, 5,0) до 1,0 (0,0, 3,0) (p = 0,024), концентрация С4-компонента комплемента повысилась с 0,13 (0,04, 0,19) до 0,43 (0,18, 0,50) г/л (p = 0,017), число антител к двуспиральной ДНК снизилось с 73,5 (11,5, 245,0) до 1,9 (0,0,40,0) МЕ/мл (p = 0,004). Деплеция в В лимфоцитах была зарегистрирована у всех пациентов через 24 и 48 нед терапии ритуксимабом. Доза преднизолона была снижена с исходной 0,80 (0,43, 1,00) мг/кг в сут до 0,20 (0,17, 0,30) через 48 нед (p = 0,025). Обострений болезни в течение 48 нед не зарегистрировано. Отмечены такие серьезные нежелательные явления, как пневмония (n = 2), нейтропения (n = 5), инфекция Herpes zoster (n = 2), гипогаммаглобулинемия (n = 8).

Background

Background. Blocking of B lymphocytes producing autoantibodies in systemic lupus erythematosus (SLE) may be an effective strategy for pathogenetic treatment, including in children.

Objective

Objective: Our aim was to assess the efficacy and safety of rituximab treatment (chimeric monoclonal antibodies to CD20) in children with severe SLE refractory to glucocorticosteroids and immunosuppressants.

Methods

Methods. We studied the case histories of children with SLE admitted to the rheumatology department of the SCCH between 2004 and 2013. The treatment results were assessed by the SELENA SLEDAI Disease Activity Index, Damage Index scale, and dynamics of the values of laboratory disease activity indices.

Results

Results. We analyzed the results of rituximab treatment in 12 patients for 24 weeks, 11 of them — for 48 weeks. The preparation was administered intravenously at a dose of 375 mg/m2 of the body surface area to administer 4 times weekly (n = 10) or 2 times with an interval of 2 weeks (n = 2). After 48 weeks of rituximab treatment, SELENA SLEDAI index values decreased from 16 (11, 21) to 1 (0, 2) (p < 0.001), Damage Index — from 3.5 (1.0, 5.0) to 1.0 (0.0, 3.0) (p = 0.024), complement component C4 concentration increased from 0.13 (0.04, 0.19) to 0.43 (0.18, 0.50) g/l (p = 0.017), the number of antibodies to double-stranded DNA decreased from 73.5 (11.5, 245.0) to 1.9 (0.0, 40.0) IU/ml (p = 0.004). Depletion of B lymphocytes was recorded in all patients after 24 and 48 weeks of rituximab treatment. Prednisolone dose was reduced from the initial 0.80 (0.43, 1.00) mg/kg per day to 0.20 (0.17, 0.30) after 48 weeks (p = 0.025). Disease exacerbations during 48 weeks have not been reported. Such serious adverse events as pneumonia (n = 2), neutropenia (n = 5), Herpes zoster infection (n = 2), hypogammaglobulinemia (n = 8) were noted.

Conclusion

Conclusion. High efficacy and satisfactory risk-benefit profile of rituximab treatment in children with severe SLE refractory to glucocorticosteroids and immunosuppressants have been shown.

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The authors declare that there are no conflicts of interest present.